Supramolecular Influence on Keto-Enol Tautomerism and Thermochromic Properties of o-Hydroxy Schiff Bases

This work presents a study on thermo-optical properties of three Schiff bases (imines) in the solid state. The Schiff bases were obtained by means of mechanochemical synthesis using monosubstituted o-hydroxy aromatic aldehydes and monosubstituted aromatic amines. The keto-enol tautomerism and proton transfer via intramolecular O∙∙∙N hydrogen bond of the reported compounds was found to be influenced more by supramolecular interactions than by a temperature change. All products were characterised by powder X-ray diffraction (PXRD), FT-IR spectroscopy, thermogravimetric (TG) analysis and differential scanning calorimetry (DSC). Molecular and crystal structures of compounds 1, 2 and 3 were determined by single crystal X-ray diffraction (SCXRD). The molecules of 1 appear to be present as the enol-imine, the molecules of 2 as the keto-amine tautomer and the molecules of 3 exhibit keto-enol tautomeric equilibrium in the solid state. An analysis of Cambridge structural database (CSD) data on similar imines has been used for structural comparison.


INTRODUCTION
-SUBSTITUTED imines or Schiff bases can be easily synthesized by condensation of aldehydes (or ketones) and primary amines. [1]They are a very good class of organic compounds for the investigation of faster and ecologically and economically more acceptable ways of preparation. [2,3]6][7][8] The physico-chemical, biological, pharmacological properties of N-substituted imines and their metal complexes are well recognized reasons of a widespread and continuous strong interest in their investigation. [9,10]In this big class of compounds, o-hydroxy aromatic imines are drawing special attention for many years.Their optical properties in the solid state can be switched by various stimuli, for example temperature change in thermochromic or by changing the wavelength of irradiation in photochromic Schiff bases. [11]The microscopic reasons of such macroscopic properties are still under investigation, [7,8,[12][13][14][15][16][17][18][19] and this work is one of them.There are three described mutually dependant reasons for such behaviour in the solid state: proton transfer via intramolecular O⋯N hydrogen bonds and thus the change of the tautomeric form, [12][13][14][15][16][17] the contribution of fluorescence and not only of light absorption as a consequence of the tautomeric change and the change in molecular geometry. [18][20][21][22][23] In this work, we report both the mechanochemical synthesis and the investigation of structurethermochromism correlation of three Schiff bases (Scheme 1) derived from three aromatic aldehydeso-vanillin (ovan), o-hydroxysalicylaldehyde (oOH) and p-hydroxysalicylaldehyde (pOH) and three aromatic amines -2-amino-4-methylphenol (2a4mp), 3-aminoacetophenone (3aa) and 4-aminoacetophenone (4aa).The aldehydes and amines were selected according to the

Synthesis and Characterization
In all three cases 1 mmol : 1 mmol stochiometric ratio of aldehyde and amine was used in order to obtain the Schiff base.Syntheses were performed at room temperature (RT) and at 40-60 % relative humidity.Bulk products of syntheses and recrystallization were characterized by means of PXRD, DSC, TGA and FT-IR.The structural investigations were performed at RT (298 K) and LT (110 K).
Neat grinding (NGam) of solid reactants (ovan and 4aa) in an agate mortar lead first to a moist paste-like reaction mixture and then to an orange powder after three minutes (Figure S1a)).][30][31][32][33] However the conversion to compound 1 was incomplete according to the PXRD data as can be seen in Figure 1 (left).For that reason, the reaction was repeated in a mortar by means of liquid-assisted grinding (LAGam) using 20 μL acetonitrile (MeCN) yielding in complete conversion of reactants into compound 1.
Neat grinding of oOH and 2a4mp in a mortar for 11 minutes did not give any change in colour or aggregation state of the reaction mixture and for that reason a catalytic amount (20 μL) of tetrahydrofuran (thf) was added (Figure S2a)).In three minutes of further grinding an orange powder was obtained.PXRD experiments have shown that a complete conversion of reactants to product, compound 2, was achieved as can be seen in Figure 1 (middle).[30][31][32][33] The reaction mixture starts to change its colour already after one minute of NGam of pOH and 3aa (Figure S3a)).][29][30][31][32] The paste forms slowly and starts to solidify after about 13 minutes of grinding.Finally, a red powder of compound 3 was obtained after 14 minutes of grinding and there were no traces of reactants in it, revealed by PXRD experiments (Figure 1 (right)).

Structural Investigations
PXRD experiments were performed on a PHILIPS PW 1840 X-ray diffractometer with CuKα1 (1.54056 Å) radiation at 40 mA and 40 kV.The scattered intensities were measured with a scintillation counter.The angular range (2 ) was from 5 to 45° with steps of 0.02°, and the measuring time was 0.5 s per step.The data collection and analysis were performed using the program package Philips X'Pert.SCXRD experiments were performed at 298 K (RT) and 110 K (LT) in order to explore thermochromic behaviour of these compounds using an Oxford Diffraction Xcalibur Kappa CCD X-ray diffractometer with graphite-monochromated MoKα (λ = 0.71073 Å) radiation (for details see the ESI).

Thermal Analysis
The measurements were performed on a Mettler Toledo DSC823e and on a Mettler Toledo TGA/SDTA 851 module.with the numbering scheme.

Spectroscopic Study on Recrystallized Material
Infrared spectra were recorded on a PerkinElmer Spectrum Two FTIR spectrophotometer using the KBr pellet method.
For details see ESI.

RESULTS AND DISCUSSION
CSD [24] Data Analysis Data obtained by means of the search are comprised in Table S6 and the structural motifs used for CSD [24] search are shown in top row of the table (see ESI).The search revealed that there are 96 entries in total, 47 entries that correspond to Schiff bases derived from ovan, 40 entries for ones derived from oOH and 9 for pOH.The scatterplot of d(C7-N1) vs. d(C2-O1) of all data obtained by the CSD search is shown in Figure 2 while Figure 3 shows a diagram of incidence of imines being (non)planar e.g.having the dihedral angle ≤ 25° ≥.
Using the data reported by Allen et.al. [25] (Table S7 in ESI) and the data obtained by the search we can conclude that the imines derived from ovan (Figure 2, red dots) and pOH (Figure 2, green dots) are mostly in enol-imine tautomeric form in the solid state.However, the Schiff bases derived from oOH (Figure 2, blue dots) in most cases have intermediary values of C2-O1 and C7-N1 bond lengths.According to the bond length criterion, compound 1 is a pure enol-imine (and is so) while compound 2 and 3 should exhibit keto-enol tautomerism in the solid state.Such behaviour was found only for compound 3 and compound 2 is a keto-amine, opposite than one can expect and conclude from Figure 2.   [24] search.Red dots -ovan imines; blue dots -oOH imines; green dots -pOH imines; pink heartscompound 1, yellow hearts -compound 2; black heartscompound 3; blue line -limiting values of d(C7-N1) and d(C2-O1) for an enol-imine, [25] red line -limiting values of d(C7-N1) and d(C2-O1) for a keto-amine, [25] green lineaverage values of d(C7-N1) and d(C2-O1). [25][14][15][16][17][18][19][20][21][22][23] A molecular overlay of molecules of all three Schiff bases is given in Figure 3b and shows the small deviation of the molecules from planarity.The influence of temperature on the planarity of these three imines is neglectable.
Most of the imines found reported in the CSD are planar (Table S6) and as such should show thermochromic properties, but we emphasize once again that this criterion should be taken prudently into consideration.Once again, we prove here that though the dihedral angles in molecules of 1-3 are well < 25°, compound 3 is not thermochromic.

Structural Analysis
Single crystals suitable for SCXRD experiments were obtained by slow evaporation of solvent (MeCN for 1 and 2 and thf for 3).General and crystallographic data for all three compounds are given in ESI (Tables S2-S4) and CCDC 1442712-1442714 contain crystallographic data for this paper.Table 1 comprises data on C7-N1 and C2-O1 bond lengths and values of dihedral angles (Φ) at RT and LT while the details on intra-and intermolecular contacts are given in Table 2 and Table 3, respectively.
Compound 1 crystallizes in monoclinic system in the general position of P21/c space group with four molecules per unit cell.The molecular formula with the numbering scheme of 1 is given in Figure S4.As stated prior in text, the molecules of 1 are in enol-imine form both at RT and LT.The hydrogen atom H1 is located closer to the oxygen O2 atom then to the nitrogen atom N1 as can be seen in δF maps calculated through N1-C7-C1-C2-O1 chelate ring of 1 at RT and LT (Figure 4).The crystal of compound 1 changes its colour from red to yellow upon cooling (Figure 4).The values of C2-O1 and C7-N1 are also in agreement with enol-imine form at both temperatures (Table 2).
The crystal of 2 changes its colour from red at RT to orange-yellow at LT (Figure 4).The molecules of 2 crystallize in orthorhombic system, in general position of P212121 space group with four molecules per unit cell.The molecular formula with the numbering scheme of 2 is given in Figure S5.The H1-atom (at both temperatures) is located closer to the N1 than to the O1 atom in the intermolecular H-bond (Figure 4).In this case the O1•••N1 distance is approximately 0.045 Å shorter than in 1 (Table 2).The position of H1 indicates that the molecules of compound 2 Table 1.C7-N1 and C2-O1 bond lengths and dihedral angle (Φ) values in compounds 1-3.are in keto-amine tautomeric form both at RT and LT while according to Figure 2 keto-enol tautomeric equilibrium would be expected Compound 2 shows reversible thermochromic properties (Figure 4) although a bit weaker than compound 1.
In the case of compound 3, two molecules per unit cell crystallize in P1 _ space group of the triclinic system.The influence of the temperature change on the colour was not found in this case, however there is an influence on the tautomeric equilibrium (Figure 4).At RT about 60 % of the molecules are in enol-imine form and 40 % in keto-amine form (Figure 1).By lowering down the temperature to 110 K the position of the tautomeric equilibrium changes and about 50 % of the molecules are in enol-imine and 50 % in keto-amine form.The split position of the H1-atom in the intramolecular O1•••N1 hydrogen bond can be easily seen in Figure 4.The C2-O1 bond length at both temperatures is on the limiting value of the intermediary and the tabulated value (ESI, Table S7) for a pure enol-imine form (Figure 2). [25]The N1-C7 bond length points to an equilibrium of both tautomers.The intramolecular H-bond is even a bit shorter than in 1 and 2 (Table 3).

Supramolecular Influences
A detailed study of the differences in crystal packing of these three Schiff bases has led us to the opinion that the thermo-optical properties and keto-enol tautomerism are governed by supramolecular influences.Table 3. Intermolecular H-bond parameters in compounds 1-3 (D = donor atom, A = acceptor atom).5).In this case the O1 atom participates in a strong intermolecular bond mentioned above as a hydrogen bond acceptor.That led to "pushing" the H1-atom away from the parent oxygen O1 to the N1-atom.The intramolecular N1-H1•••O1 bond is just a bit shorter (Table 2) than the intermolecular O2-H2•••O1 interaction.Consequently, O1 atom is under supramolecular impact resulting in keto-amine tautomeric form.
In the case of compound 3 there is a tautomeric equilibrium The O1 atom participates in O2-H2•••O1 interaction as well.However, here the O2•••O1 distance is a bit longer than in 2 (Table 3).This apparently facilitates the proton transfer from the parent oxygen O1 atom to the nitrogen N1 atom and vice versa and is crucial for the ketoenol tautomerism in this compound.The molecules of 3 form 1D-chains via [010] direction which are further connected into 3D-networks by means of four C-H•••O (Table 3) and by π•••π interactions (3.3-3.4Å), Figure 5.
In compound 3, the supramolecular influence is greater than in 1 and milder than in 2 and consequently keto-enol tautomeric equilibrium can be observed.The described interactions in compounds 1-3 can be seen in 2D-fingerprint plots obtained from Hirshfeld surfaces [34] (Figure 6).

Thermal Study
The thermal properties of the compounds were studied using DSC and TGA.This study, accompanied by PXRD experiments, revealed that compound 1 undergoes an endothermic polymorphic transition upon heating (Figure S10, S11) from form I reported here to form II. Compound  Intermolecular interaction strength vs. melting point as structure-property correlation has shown to be true in the case of the three compounds reported here.Table 4

comprises the values of melting points and the values of means of d(D-H•••A).
In the case of compounds 1-3, the smaller the value of ̅ the higher the melting onset meaning that the number and strength of the intermolecular interactions present directly impacts on the thermal stability i.e. melting of the material.
According to our experience and work on numerous examples of this kind of compounds this kind of structureproperty correlation should not be generalised.

CONCLUSION
Herein, we report three o-hydroxy imines obtained by means of grinding.In the solid state, the molecules of compound 1 (ovan4aa) are in enol-imine tautomeric form, compound 2 (oOH2a4mp) was obtained as a keto-amine while there is a keto-enol tautomeric equilibrium in compound 3 (pOH3aa).The tautomerism of 1 and 2 is not influenced greatly by a temperature change although they do show thermochromic properties.On the other hand, there is a slight decrease in the population of molecules in enol-imine form with cooling but the colour change was not observed.We have demonstrated a huge effect of the type and strength of hydrogen bonds that involve the oxygen atom O1 on the keto-enol tautomerism.This has proved that the proton transfer via intramolecular O•••H•••N hydrogen bond is influenced strongly by supramolecular effects rather than by a change in molecular geometry in this type of compounds and that there is finally no doubt about the causes of keto-enol tautomerism in this class of compounds in the solid state.
The presented results are important for the understanding of supramolecular influences on macroscopic properties of imines, as well as on the possible design of other similar compounds that could be used as dyes or pigments.This study states out the importance of further research on this class of organic compounds in order to get better and detailed insight in solid-state and materials chemistry.

Materials
All reagents and solvents were purchased from commercial sources and used as received.Table S2 comprises all starting materials and solvents used for syntheses, crystallization or liquidassisted grinding experiments.
Table S1 Starting materials used for various experiments.

Mechanochemical synthesis accompanied by PXRD experiments
All grinding experiments were performed in an agate mortar at RT and 40-50 % relative humidity.The required grinding time in the agate mortar was determined empirically when the colour of the reaction mixture stopped changing.PXRD experiments were performed on all powder products obtained by grinding to check if the condensation reaction of the aldehyde and amine yielded in product.

Synthesis of compound 1
Equimolar quantities of ovan (0.153 g, 1 mmol) and 4aa (0.135 g, 1 mmol) were first ground in an agate mortar at 25 °C.After 40 s an orange paste appears which solidifies in an orange powder after 3 minutes (Figure S1 A)).The PXRD data of that material revealed some traces of unreacted material so the reaction was repeated but by means of LAG in presence of 20 μL of MeCN added in the reaction mixture.Orange powder of compound 1 (ovan4aa) was obtained again and the PXRD data of the powder product is in good agreement with the calculated pattern.Small amount of the obtained powder was dissolved in acn and the single crystals suitable for SCXRD experiments were obtained by slow evaporation of solvent.

Powder X-Ray diffraction experiments
Powder X-ray diffraction (PXRD) experiments were performed on a PHILIPS PW 1840 X-ray diffractometer with CuKα1 (1.54056 Å) radiation at 40 mA and 40 kV.The scattered intensities were measured with a scintillation counter.The angular range (2 ) was from 5 to 45° with steps of 0.02°, and the measuring time was 0.5 s per step.The data collection and analysis were performed using the program package Philips X'Pert. [1,2,3]

Single Crystal X-Ray diffraction experiments
Crystal and molecular structures were determined at 298 and 110 K using single crystal X-ray diffraction.Diffraction measurements were made on an Oxford Diffraction Xcalibur Kappa CCD X-ray diffractometer with graphite-monochromated MoK ( = 0.71073 Å) radiation and the instrument was operated using CrysAlis CCD and RED. [4]The data sets were collected using the  scan mode over the 2 range up to 54°.The structures were solved by direct methods and refined using the SHELXS and SHELXL programs, respectively. [5]The structural refinement was performed on F 2 using all data.The hydrogen atoms not involved in hydrogen bonding were placed in calculated positions and treated as riding on their parent atoms [C-H = 0.93 Å and Uiso(H) = 1.2 Ueq(C); C-H = 0.97 Å and Uiso(H) = 1.2 Ueq(C)] while the others were located from the electron difference map.All calculations were performed using the WinGX crystallographic suite of programs. [6]The data concerning the results of the crystallographic experiments are listed in Table S2.Further details are available from the Cambridge Crystallographic Centre (1442712-1442714). [7]Molecular structures of compounds are presented using ORTEP-3 [8] and are presented in Figures S4-S6 and their packing diagrams were prepared using Mercury. [9]5.Thermal study

DSC experiments
The measurements were performed on a Mettler Toledo DSC823 e module in sealed aluminium pans (40 μL), heated in flowing nitrogen (200 mL min −1 ) at a rate of 10 °C min −1 .The data collection and analysis was performed using the program package STAR e Software 9.01.[ 10 ].
Samples of compound 1, were heated to fifteen different temperatures (60 °C, 120-135 °C) and then kept at those selected temperatures for 5 minutes as well.After that, the samples were cooled to 25 °C and PXRD measurements on the obtained material were done revealing that form I of compound 1 undergoes a temperature induced transformation at temperatures between 121 and 131 °C.

TG experiments
The measurements were performed on a Mettler Toledo TGA/SDTA 851 module in sealed aluminium pans (40 μL), heated in flowing nitrogen (200 mL min −1 ) at a rate of 10 °C min −1 .The data collection and analysis was performed using the program package STAR e Software 9.01.[ 11 ].

FT-IR spectroscopy
Infrared spectra were recorded on a PerkinElmer Spectrum Two FTIR spectrophotometer using the KBr pellet method.The data collection and analysis was performed using the program package PerkinElmer Spectrum 10.4.2.279 [12] Table S5 comprises data for the characteristic stretching bands for 1, 2 and 3.       Figure S13 TGA and SDTA curves of recrystallized material of compound 3.

Figure 3 .
Figure 3. a) A diagram of incidence of imines being (non)planar e.g.having the dihedral angle ≤ 25° ≥; b) a molecular overlay of 1 (blue), 2 (red), and 3 (purple) -blue and yellow squares represent planes in which the aromatic moieties lye, hydrogen atoms were omitted for clarity.

1
is stable up to 120 °C.From 121 °C to 131 °C it transforms to, for now, an unknown form, form II, which crystallizes upon cooling to 25 °C (Figure 7).At temperatures above 132 °C the decomposition of 1 takes place at temperatures above 260 °C.The DSC curve of compound 2 has an endothermic peak with an onset at 225 °C which corresponds to melting of 2. Starting at approx.250 °C compound 2 decomposes exothermally (Figure S10, S12).Compound 3 starts to melt at 157 °C and decomposes exothermally above 200 °C (Figure S10, S13).

1- 3 Figure 7 .
Figure 7. PXRD patterns of 1 heated up to a selected temperature and then cooled back to room temperature showing polymorphic transition at 121 °C and 131 °C.

2. 2 .
Thermal ellipsoid plots with crystallographic labelling scheme RT LT Figure S4 Thermal ellipsoid (50 %) plot of compound 1 molecule with the atom-labelling scheme.Dashed line indicates intramolecular interaction.RT LT Figure S6 Thermal ellipsoid (50 %) plot of compound 3 molecule showing the atom-labelling scheme and indicating the occupancy of the hydrogen atom.Dashed line indicates intramolecular interactions.

Figure S11
Figure S11TGA and SDTA curves of recrystallized material of compound 1.

Figure S12
Figure S12 TGA and SDTA curves of recrystallized material of compound 2.

Figure S15 IR spectrum of compound 2 .Figure S16
Figure S15 IR spectrum of compound 2.

Table S2
General and crystallographic data for 1 at 298 and 110 K.

Table S3 .
General and crystallographic data for 2 at 298 and 110 K.

Table S4 .
General and crystallographic data for 2 at 298 and 110 K.

e SW 10.00 METTLER TOLEDO 2.5. Results of FT-IR spectroscopic measurements Figure
S14 IR spectrum of compound 1.

Table S5
Characteristic stretching bands for 1, 2 and 3 found in the FT-IR spectra.

Table S6
Data obtained from the CSD on d(C7-N1), d(C2-O1) and Φ for imines derived from ovan (red data), oOH (blue data) and pOH (green data).Structural motifs used for searches are given in top row.

. Values of single and double bonds according to tabular values used often for tautomer selection Table S7 Generally
accepted values of single and double bonds according to F. H. Allen et al., J. Chem.Soc.Perkin Trans.II, 1987, S1-S19.